Ancillary (or spectator) ligand-metal coordination complexes (e.g., organometallic complexes) and compositions are useful as catalysts, additives, stoichiometric reagents, monomers, solid state precursors, therapeutic reagents and drugs. Ancillary ligand-metal coordination complexes of this type can be prepared by combining an ancillary ligand with a suitable metal compound or metal precursor in a suitable solvent under suitable reaction conditions. The ancillary ligand may contain functional groups that bind to the metal center(s), remain associated with the metal center(s), and therefore provide an opportunity to modify the steric, electronic and chemical properties of the active metal center(s) of the complex.
Certain known ancillary ligand-metal complexes and compositions are catalysts for reactions such as oxidation, reduction, hydrogenation, hydrosilylation, hydrocyanation, hydroformylation, polymerization, carbonylation, isomerization, metathesis, carbon-hydrogen activation, carbon-halogen activation, cross-coupling, hetero cross-coupling, Friedel-Crafts acylation and alkylation, hydration, amination, aryl amination, dimerization, trimerization, oligomerization, Diels-Alder reactions and other transformations.
One example of the use of these types of ancillary ligand-metal complexes and compositions is in the field of cross-coupling reactions. The palladium-catalyzed cross-coupling reactions of aryl-bromides, iodides, and triflates with alkyl or aryl-boron compounds provide a general and efficient route to a wide variety of substituted alkylphenyl or biphenyl compounds, and have now been extensively developed. See Suzuki, A. in Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; Chapter 2, pp. 49-97, which is incorporated herein by reference. See also U.S. Pat. Nos. 5,550,236 and 5,756,804, both of which are incorporated herein by reference.
However, the related palladium-catalyzed reactions of the comparatively inexpensive and readily available aryl chlorides, which represent the most attractive candidates for industrial applications of these reactions, have been underdeveloped. See Old, D. W., Wolfe, J. P., Buchwald, S. L., J. Am. Chem. Soc. 1998, 120, 9722-9723; and Littke, A. F., Fu, G. C., Angew. Chem. Int. Ed. Eng. 1998, 37, 3387-3388, which are both incorporated herein by reference. In particular, Buchwald et al. in the above referenced paper note that certain dicycloalkyl phosphine ligands are "not effective" for these palladium-catalyzed reactions. J. Am. Chem. Soc., 1998 at 9723. In the supplemental material to that paper, Buchwald et al. disclose that in a palladium-dicyclohexylphenylphosphine catalyzed Suzuki cross-coupling reaction, the turn over number (TON) was about 9 after 2 days, giving a turn over frequency (TOF) of about 0.19.
This invention thus surprisingly demonstrates that improved catalytic activity can indeed be obtained with the exact ligands and catalyst systems that were previously characterized as "not effective." Compounds prepared according to the invention are suitable for use as precursors for pharmaceuticals, cosmetics, fungicides, herbicides, dyes, detergents, and polymers, including additives for these. Compounds prepared according to the invention are, in particular, valuable precursors for angiotensin II inhibitors. See Drugs of the Future 1993, 18, 428-432.